title: Rett syndrome: from the gene to the disease.
abstract: Rett syndrome (RTT, MIM No. 312750) is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation. It is transmitted as an X-linked dominant trait, therefore almost exclusively affecting females. About 80% of RTT cases are sporadic caused by mutations in the MECP2 gene located on Xq28. The gene codes for two isoforms of the methyl-CpG-binding protein (MeCP2, MeCP2B) which are involved in transcriptional silencing through DNA methylation. The gene has 4 exons. The fourth one is the largest. Almost all mutations in MECP2 occur de novo. Although mutations are dispersed throughout the gene, about 67% of all MECP2 mutations, caused by C>T transitions at 8 CpG dinucleotides, are located in the third and fourth exon. The most common mutation is R168X. So far, there is no clear evidence on genotype-phenotype correlations. There are also reports claiming that the same mutation can provoke different phenotypes. It was shown that MeCP2 can silence certain genes. One of them, brain-derived neurotrophic factor, is essential for neural plasticity, learning and memory. This discovery revealed the role of MeCP2 in the control of neuronal activity-dependent gene regulation and suggested that the pathology of RTT may result from deregulation of this process.
authors.affiliation: Rudjer Boskovic Institute, Division of Molecular Medicine, Zagreb, Croatia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Matijevic
authors.forename: Jelena
authors.initials: J
authors.lastname: Knezevic
authors.forename: Marko
authors.initials: M
authors.lastname: Slavica
authors.forename: Jasminka
authors.initials: J
authors.lastname: Pavelic
mesh_terms: D005838:Genotype; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D015518:Rett Syndrome / Q000235:genetics* / Q000473:pathology*
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2